Efficacy and Safety of Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF)-Containing Regimens in Participants With Chronic Hepatitis B Virus (HBV) Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant

NCT02862548 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-320-3912ACTRN12616000898459
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF)-containing regimens at Week 24 in participants with chronic hepatitis B virus (HBV) infection and Stage 2 or greater chronic kidney disease who have received a liver transplant.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) at Week 24 Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation

  Baseline, Week 24

• Percentage of Participants With HBV DNA < 20 IU/mL at Week 24

  Week 24

Secondary Outcomes (8)

• Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24

  Baseline, Week 24

• Percent Change From Baseline in Hip BMD at Week 48

  Baseline, Week 48

• Percent Change From Baseline in Spine BMD at Week 24

  Baseline, Week 24

• Percent Change From Baseline in Spine BMD at Week 48

  Baseline, Week 48

• Change From Baseline in Serum Creatinine at Week 24

  Baseline, Week 24

Study Arms (3)

TAF

EXPERIMENTAL

TAF 25 mg once daily for 48 weeks

Drug: TAF

TDF-Containing Regimens

ACTIVE COMPARATOR

TDF alone or in combination with other approved antivirals per local practice for 48 weeks

Drug: TDF; Drug: Other approved antivirals

Optional Treatment Extension Phase

EXPERIMENTAL

After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks.

Drug: TAF

Interventions

TAF DRUG

Tablet administered orally

Also known as: Vemlidy®

Optional Treatment Extension Phase; TAF

TDF DRUG

Tablet administered orally

TDF-Containing Regimens

Other approved antivirals DRUG

Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice

TDF-Containing Regimens

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
• Documented evidence of chronic HBV infection prior to transplantation
• Primary or secondary (re-transplant), liver alone or liver and kidney transplant recipient from deceased or living donor
• Liver Transplant ≥ 12 weeks prior to screening
• Maintained on TDF alone or in combination with other approved antivirals for HBV prophylaxis or treatment
• Have been on approved HBV oral antiviral (OAV) treatment for at least 12 weeks post-transplant prior to screening, with HBV DNA \< lower limit of quantification (LLOQ) at screening
• Screening estimated glomerular filtration rate using the chronic kidney disease epidemiology collaboration (eGFR\_CKD-EPI) \< 90 ml/min/1.73m\^2
• Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Women considered of child bearing potential must have a negative serum pregnancy test at Screening and a negative urine test at Baseline before dosing
• Must be willing and able to comply with all study requirements

You may not qualify if:

• Multi-organ transplant that includes heart or lung recipient (participants who have their liver transplant as part of a liver-kidney dual transplant are eligible to enroll)
• Participants with history of de novo or recurrent hepatocellular carcinoma (HCC) post-transplant and at screening
• Histological evidence of unresolved transplant rejection
• Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
• Participants meeting any of the following laboratory parameters at screening:
• Alanine aminotransferase (ALT) \> 10 × the upper limit of normal (ULN)
• International normalized ratio (INR) \> 1.5 × ULN unless the participant is stable on anticoagulant regimen affecting INR
• Albumin \< 3.0 g/dL
• Direct bilirubin ≥ 4 × ULN
• Platelet count \< 50,000/mL
• Co-infection with HIV or hepatitis C virus (HCV)
• Recent (within 4 weeks of Screening) episode or infection requiring systemic antibiotics
• Use of any prohibited medications listed within 28 days of the Baseline/Day 1 visit
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (e.g., basal cell skin cancer, etc.) or hepatocellular carcinoma. Participants under evaluation for possible malignancy are not eligible
• Significant cardiovascular, pulmonary, or neurological disease

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Auckland City Hospital

Auckland, New Zealand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: September 16, 2016
• Primary Completion: February 8, 2018
• Study Completion: May 5, 2021
• Last Updated: June 8, 2022
• Results First Posted: February 26, 2019

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

NZ (1)